Abstract
Objective
The purpose of this study was to evaluate plaque characteristics of culprit and non-culprit lesions in ST-elevation myocardial infarction (STEMI) patients at the index procedure and 10 months later using iMap intravascular ultrasound (IVUS).
Background
The exact site of the plaque rupture or erosion in coronary arteries with subsequent thrombosis cannot be precisely defined. Our hypothesis is that in STEMI patients angiographically guided stenting could fail to identify necrotic tissue and thus may leave an uncovered significant amount of vulnerable plaque.
Methods
In 63 consecutive STEMI patients the culprit artery was analyzed with iMap IVUS at the time of the index procedure and 10 months later. The most stenotic culprit segment was compared to the segment proximal to the culprit lesion.
Results
A high percentage of necrotic tissue was observed in the culprit lesion and a comparatively lower percentage of necrotic tissue was observed in the non-culprit lesions proximal to the culprit at the index procedure by iMap IVUS (31.9% ± 10.0% vs 27.8% ± 11.8%, p = 0.012). The proportion of necrotic tissue in the segment proximal to the culprit lesion was unchanged at 10-month follow-up (27.1% ± 11.9% vs 25.5% ± 12.8%, p = 0.147). The percentage of lipidic tissue in the proximal segment decreased at 10-month follow-up (9.8% ± 2.9% vs 8.8 ± 3.0%, p = 0.009).
Conclusions
In STEMI patients, culprit lesion segments and non-culprit segments contain high proportions of necrotic tissue. However, a comparatively higher proportion of necrotic tissue was found in the culprit lesions according to iMap IVUS. The percentage of necrotic tissue remained high at 10-month follow-up in both culprit and non-culprit segments.
1
Introduction
Primary PCI with stenting is the cornerstone of treatment in patients with ST-elevation myocardial infarction (STEMI) . Pathology studies have shown that ruptured plaques typically have a large necrotic core and a disrupted fibrous cap with thrombus often propagating from the rupture site . Plaque rupture sites leading to clinical events are often found proximal to the most severe site of luminal obstruction by angiography. Thus angiography guided intervention may leave the site of plaque rupture or erosion uncovered. iMap intravascular ultrasound (iMap; Boston Scientific Corp, Fremont, CA, USA) is a new software package for assessing plaque composition (fibrotic, lipidic, necrotic, calcific) according to backscattered ultrasound frequency spectrum .
The purpose of the study was to evaluate plaque characteristics of the culprit lesion and of the coronary segment proximal to the culprit lesion using iMap intravascular ultrasound (IVUS) at index procedure and to compare the qualitative characteristics of plaque composition 10 months later in ST-elevation myocardial infarction patients.
2
Methods
2.1
Study population and design
From September 2009 to February 2010, 63 patients were enrolled in a single-center, prospective study of primary percutaneous coronary intervention (PPCI) in patients with STEMI at the Latvian Centre of Cardiology, Pauls Stradins Clinical University Hospital.
STEMI was diagnosed by the presence of prolonged chest pain (> 30 min) with ST-segment elevation of > 0.1 mV in two or more adjacent standard leads or > 0.2 mV in two or more adjacent precordial leads or left bundle branch block on standard electrocardiogram. Patients presenting within 12 h of the onset of symptoms, without pre-hospital thrombolytic therapy and no previous intervention in the culprit vessel and no previous history of coronary artery bypass surgery were eligible for enrollment.
Cardiogenic shock was defined as hypotension (systolic blood pressure < 90 mm Hg or a drop of a mean arterial pressure by > 30 mm Hg) with evidence of peripheral hypoperfusion .
At the time of the index hospitalization, all study patients underwent coronary angiography and IVUS with iMap tissue characterization of the culprit artery. Follow-up angiography and IVUS iMap tissue characterization of the culprit artery were performed 10 months later. Six cardiac deaths were documented, four of them occurred during the index hospitalization due to the cardiogenic shock and two patients had cardiac death during the follow-up period. Additionally, during the follow-up period two patients had non cardiac death: one patient had cerebrovascular death and another patient died of urinary bladder carcinoma. Of the remaining 55 patients, 49 underwent coronary angiography and IVUS with iMap tissue characterization of the culprit artery after 292.8 ± 48.0 days, and 6 asymptomatic patients refused.
2.2
Procedures and adjunctive medical therapy
All PPCI procedures were performed through a femoral or radial approach using a 6F or 7F guiding catheter. After conventional wire crossing of the culprit lesion and thrombus aspiration the ultrasound Imaging Catheter Atlantis SR Pro (40-MHz, mechanical-type transducer, 3.2F, Boston Scientific Corporation, Natick, MA, USA) was advanced > 10 mm beyond the culprit lesion and was pulled back to a point > 20 mm proximal to the lesion using motorized transducer pullback at 0.5 mm/s pre- and post-intervention. The IVUS data were stored on a hard disk for offline analysis, which was performed independently by two analysts. Quantitative analysis of grayscale IVUS images was performed according to the criteria of the American College of Cardiology Clinical Expert Consensus Document on IVUS . We defined two segments of interest during IVUS analysis: the culprit segment and the segment immediately proximal to the culprit lesion. The culprit segment was defined in the first IVUS pullback as the segment with the greatest stenosis severity. The proximal segment was defined in the second IVUS pullback as the 20-mm segment immediately proximal to the stent edge or the segment from the proximal edge of the stent to the ostium of the vessel, if < 20 mm in length. The same definition for proximal segment iMap IVUS analysis was applied at the 10-month follow-up. Virtual plaque assessment of both, the proximal segment and culprit segment was performed with iMap software (QIvus 2.0; Medis medical imaging systems, Leiden, the Netherlands). The percentage of each tissue component was determined. Plaques unsuitable for analysis because of acoustic shadowing behind calcification or wire artifact was removed automatically by iMap software.
According to operator discretion either drug-eluting or bare-metal stents were used. All patients were treated with aspirin 325 mg and clopidogrel 600 mg prior to PPCI and dual-antiplatelet therapy was prescribed for 1 year. During PPCI, patients were anticoagulated with unfractioned heparin (a bolus 80 U/kg) or low molecular heparin enoxaparin (a bolus 1 mg/kg). Sixty-three (96.9%) patients received GP IIb/IIIa receptor antagonists (abciximab, tirofiban or eptifibatide) with a bolus dose and continued infusion 12–24 h post-procedure.
2.3
Angiographic analyses
Angiographic analyses included coronary Thrombolysis in Myocardial Infarction (TIMI) flow grading and final myocardial blush grading . Angiographic assessment was performed by two independent angiographers and all angiographic endpoints were evaluated before and after PPCI. We defined angiographic no-reflow as a final TIMI flow of ≤ 2.
2.4
Blood lipid analyses
Venous blood for lipid assessment was collected during the index hospitalization and during the hospital stay at 10-month follow-up. Percent changes in low-density lipoprotein cholesterol (LDL-C) were calculated. All patients at 10-month follow-up were divided into two groups: group 1, reduction of LDL-C and group 2, increase of LDL-C.
2.5
Data collection
Demographic, clinical and procedural data, angiography and IVUS outcomes at the index procedure and at 10-month follow-up were collected and entered into a prospective database.
2.6
Statistical analyses
Data analysis was performed with the Statistical Package for Social Sciences (SPSS) software for Windows version 17.0.1 (Chicago, IL, USA). Categorical data were presented as frequencies and percentages; continuous variables were expressed as the mean ± standard deviation (SD). Continuous variables were compared with analysis of variance (ANOVA) test. A p value < 0.05 was considered statistically significant.
2.6.1
Inclusion criteria
- •
More than 18 years of age
- •
Signed informed consent
- •
Onset of symptoms of acute myocardial infarction > 30 min and < 12 h
- •
ST-segment elevation of > 0.1 mV in two or more adjacent standard leads or > 0.2 mV in two or more adjacent precordial leads or left bundle branch block on standard electrocardiogram
2.6.2
Exclusion criteria
- •
Non-cardiac illness associated with life expectancy of less than 1 year
- •
Pre-hospital thrombolytic therapy
- •
Previous PCI in infarct related artery
- •
Patients with history of cardiovascular bypass surgery
- •
TIMI flow = 0 after thrombus aspiration
- •
Failure to advance the IVUS catheter through the culprit lesion
2
Methods
2.1
Study population and design
From September 2009 to February 2010, 63 patients were enrolled in a single-center, prospective study of primary percutaneous coronary intervention (PPCI) in patients with STEMI at the Latvian Centre of Cardiology, Pauls Stradins Clinical University Hospital.
STEMI was diagnosed by the presence of prolonged chest pain (> 30 min) with ST-segment elevation of > 0.1 mV in two or more adjacent standard leads or > 0.2 mV in two or more adjacent precordial leads or left bundle branch block on standard electrocardiogram. Patients presenting within 12 h of the onset of symptoms, without pre-hospital thrombolytic therapy and no previous intervention in the culprit vessel and no previous history of coronary artery bypass surgery were eligible for enrollment.
Cardiogenic shock was defined as hypotension (systolic blood pressure < 90 mm Hg or a drop of a mean arterial pressure by > 30 mm Hg) with evidence of peripheral hypoperfusion .
At the time of the index hospitalization, all study patients underwent coronary angiography and IVUS with iMap tissue characterization of the culprit artery. Follow-up angiography and IVUS iMap tissue characterization of the culprit artery were performed 10 months later. Six cardiac deaths were documented, four of them occurred during the index hospitalization due to the cardiogenic shock and two patients had cardiac death during the follow-up period. Additionally, during the follow-up period two patients had non cardiac death: one patient had cerebrovascular death and another patient died of urinary bladder carcinoma. Of the remaining 55 patients, 49 underwent coronary angiography and IVUS with iMap tissue characterization of the culprit artery after 292.8 ± 48.0 days, and 6 asymptomatic patients refused.
2.2
Procedures and adjunctive medical therapy
All PPCI procedures were performed through a femoral or radial approach using a 6F or 7F guiding catheter. After conventional wire crossing of the culprit lesion and thrombus aspiration the ultrasound Imaging Catheter Atlantis SR Pro (40-MHz, mechanical-type transducer, 3.2F, Boston Scientific Corporation, Natick, MA, USA) was advanced > 10 mm beyond the culprit lesion and was pulled back to a point > 20 mm proximal to the lesion using motorized transducer pullback at 0.5 mm/s pre- and post-intervention. The IVUS data were stored on a hard disk for offline analysis, which was performed independently by two analysts. Quantitative analysis of grayscale IVUS images was performed according to the criteria of the American College of Cardiology Clinical Expert Consensus Document on IVUS . We defined two segments of interest during IVUS analysis: the culprit segment and the segment immediately proximal to the culprit lesion. The culprit segment was defined in the first IVUS pullback as the segment with the greatest stenosis severity. The proximal segment was defined in the second IVUS pullback as the 20-mm segment immediately proximal to the stent edge or the segment from the proximal edge of the stent to the ostium of the vessel, if < 20 mm in length. The same definition for proximal segment iMap IVUS analysis was applied at the 10-month follow-up. Virtual plaque assessment of both, the proximal segment and culprit segment was performed with iMap software (QIvus 2.0; Medis medical imaging systems, Leiden, the Netherlands). The percentage of each tissue component was determined. Plaques unsuitable for analysis because of acoustic shadowing behind calcification or wire artifact was removed automatically by iMap software.
According to operator discretion either drug-eluting or bare-metal stents were used. All patients were treated with aspirin 325 mg and clopidogrel 600 mg prior to PPCI and dual-antiplatelet therapy was prescribed for 1 year. During PPCI, patients were anticoagulated with unfractioned heparin (a bolus 80 U/kg) or low molecular heparin enoxaparin (a bolus 1 mg/kg). Sixty-three (96.9%) patients received GP IIb/IIIa receptor antagonists (abciximab, tirofiban or eptifibatide) with a bolus dose and continued infusion 12–24 h post-procedure.
2.3
Angiographic analyses
Angiographic analyses included coronary Thrombolysis in Myocardial Infarction (TIMI) flow grading and final myocardial blush grading . Angiographic assessment was performed by two independent angiographers and all angiographic endpoints were evaluated before and after PPCI. We defined angiographic no-reflow as a final TIMI flow of ≤ 2.
2.4
Blood lipid analyses
Venous blood for lipid assessment was collected during the index hospitalization and during the hospital stay at 10-month follow-up. Percent changes in low-density lipoprotein cholesterol (LDL-C) were calculated. All patients at 10-month follow-up were divided into two groups: group 1, reduction of LDL-C and group 2, increase of LDL-C.
2.5
Data collection
Demographic, clinical and procedural data, angiography and IVUS outcomes at the index procedure and at 10-month follow-up were collected and entered into a prospective database.
2.6
Statistical analyses
Data analysis was performed with the Statistical Package for Social Sciences (SPSS) software for Windows version 17.0.1 (Chicago, IL, USA). Categorical data were presented as frequencies and percentages; continuous variables were expressed as the mean ± standard deviation (SD). Continuous variables were compared with analysis of variance (ANOVA) test. A p value < 0.05 was considered statistically significant.
2.6.1
Inclusion criteria
- •
More than 18 years of age
- •
Signed informed consent
- •
Onset of symptoms of acute myocardial infarction > 30 min and < 12 h
- •
ST-segment elevation of > 0.1 mV in two or more adjacent standard leads or > 0.2 mV in two or more adjacent precordial leads or left bundle branch block on standard electrocardiogram
2.6.2
Exclusion criteria
- •
Non-cardiac illness associated with life expectancy of less than 1 year
- •
Pre-hospital thrombolytic therapy
- •
Previous PCI in infarct related artery
- •
Patients with history of cardiovascular bypass surgery
- •
TIMI flow = 0 after thrombus aspiration
- •
Failure to advance the IVUS catheter through the culprit lesion
3
Results
The baseline characteristics of study patients are summarized in Table 1 . Coronary angiographic findings and procedural characteristics are shown in Table 2 .
Characteristic | Value |
---|---|
Age, years | 62.9 ± 13.5 |
Male | 40 (63.5%) |
Cardiogenic shock | 7 (11.1%) |
Diabetes | 8 (12.7%) |
Hypertension | 38 (60.3%) |
Current smoker | 30 (47.6%) |
History of myocardial infarction | 6 (9.5%) |
Ejection fraction, % | 49.1 ± 8.0 |
Creatinine, μmol/l | 87.6 ± 19.9 |
Glucose, mmol/l | 9.2 ± 3.9 |
Total cholesterol, mmol/l | 5.8 ± 1.2 |
LDL-C, mmol/l | 4.0 ± 1.0 |
HDL-C, mmol/l | 1.0 ± 0.3 |
Triglyceride, mmol/l | 1.9 ± 1.2 |
Body mass index, kg/m 2 | 29.6 ± 6.1 |